Magnetic resonance imaging contrast agents can be classified according to property at a magnetic field into the following: (1) T1 contrast agents for reducing spin-lattice relaxation time T1, and thereby increasing tissue signals; and (2) T2 contrast agents for reducing spin-spin relaxation time T2, and thereby reducing tissue signals and effectively identifying whether a tissue is normal (J. Chem. Soc., Dalton Trans, 1998, 4113-4118; Helv. Chim. Acta, 2002, 85, 1033).
A typical T1 contrast agent is a metal complex having a paramagnetic metal ion and a plurality of ligands chelating the metal ion. A typical T2 contrast agent is a polymer having nanoparticles such as superparamagnetic iron oxide nanoparticles (SPIO).
Currently, the magnetic resonance imaging technology has been used in animal models for producing images showing biochemical functions at molecular or cellular levels. There are many developments on contrast agents, especially on biomolecule-targeting contrast agents. Since cardiovascular diseases have higher incidence and mortality than tumors and are the most severe diseases, many magnetic resonance imaging contrast agents for detecting vascular thrombosis of atherosclerosis or cardiovascular diseases have been developed. For example, Chinese Patent No. 101347625 discloses MRI thrombus target-directed contrast agents and the preparation method thereof, wherein a P-selectin-targeting contrast agent ((Gd-DTPA)n-BSA-PsL-EGFmAb) is provided for being coupled with epithermal growth factors (EGF) on thrombocytes. However, due to the large molecular weight, this contrast agent is not easy to enter an artery, and thus can only be used in the early stage of thrombosis. In addition, US Patent Application Publication No. 2011/0268663A discloses an intravascular contrast agent for MRI, wherein the contrast agent includes a Gd-complex attached with an amino acid unit. However, this contrast agent has poor specificity to thrombocytes, and is thus poorly identified by thrombocytes.
Matrix metalloproteases (MMPs) are proteases, and play important roles in physiology, pathology and structural construction, such as morphogenesis, angiogenesis, arthritis and tumor metastasis. It is found in the study of cardiovascular diseases that vascular smooth muscle cells move from an intermediate layer to an inner layer, and proliferate and accumulate at an inner layer of a blood vessel during atherosclerosis. While damages or thrombosis occurs at a blood vessel, matrix metalloprotease 2 are significantly expressed, and involves in the formation of atherosclerosis (Physiol Rev, 2005, 85, 1-31).